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PDBsum entry 4l7f
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Transferase/transferase inhibitor
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PDB id
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4l7f
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PDB id:
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| Name: |
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Transferase/transferase inhibitor
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Title:
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Co-crystal structure of jnk1 and ax13587
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Structure:
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Mitogen-activated protein kinase 8. Chain: a. Fragment: unp residues 7-362. Synonym: map kinase 8, mapk 8, jnk-46, stress-activated protein kinase 1c, sapk1c, stress-activated protein kinase jnk1, c-jun n- terminal kinase 1. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk8, jnk1, prkm8, sapk1, sapk1c
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Resolution:
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1.95Å
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R-factor:
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0.162
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R-free:
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0.198
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Authors:
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R.L.Walter,G.M.Ranieri,A.M.Riggs,H.Weissig,B.Li,K.R.Shreder
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Key ref:
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B.Li
et al.
(2013).
Hit-to-lead optimization and kinase selectivity of imidazo[1,2-a]quinoxalin-4-amine derived JNK1 inhibitors.
Bioorg Med Chem Lett,
23,
5217-5222.
PubMed id:
DOI:
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Date:
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13-Jun-13
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Release date:
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21-Aug-13
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PROCHECK
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Headers
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References
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P45983
(MK08_HUMAN) -
Mitogen-activated protein kinase 8 from Homo sapiens
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Seq:
Struc:
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427 a.a.
354 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 11 residue positions (black
crosses)
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Enzyme class:
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E.C.2.7.11.24
- mitogen-activated protein kinase.
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Reaction:
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1.
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L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
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2.
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L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
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L-seryl-[protein]
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+
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ATP
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=
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O-phospho-L-seryl-[protein]
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+
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ADP
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+
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H(+)
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L-threonyl-[protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Bioorg Med Chem Lett
23:5217-5222
(2013)
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PubMed id:
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Hit-to-lead optimization and kinase selectivity of imidazo[1,2-a]quinoxalin-4-amine derived JNK1 inhibitors.
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B.Li,
O.M.Cociorva,
T.Nomanbhoy,
H.Weissig,
Q.Li,
K.Nakamura,
M.Liyanage,
M.C.Zhang,
A.Y.Shih,
A.Aban,
Y.Hu,
J.Cajica,
L.Pham,
J.W.Kozarich,
K.R.Shreder.
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ABSTRACT
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As the result of a rhJNK1 HTS, the imidazo[1,2-a]quinoxaline 1 was identified as
a 1.6μM rhJNK1 inhibitor. Optimization of this compound lead to AX13587 (rhJNK1
IC50=160nM) which was co-crystallized with JNK1 to identify key molecular
interactions. Kinase profiling against 125+ kinases revealed AX13587 was an
inhibitor of JNK, MAST3, and MAST4 whereas its methylene homolog AX14373 (native
JNK1 IC50=47nM) was a highly specific JNK inhibitor.
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